POSITRON EMISSION TOMOGRAPHY SCAN

Moderator : Dr Sanjay Pandey

Presenter : Prashant Makhija

PET Scan

What it is ?

Historical background

How does it work ?

Applications in Neurology Dementia Epilepsy Movement disorders Stroke Brain tumors Others Limitations Potential future applications

What it is ?

A scanning procedure that enables visualisation of the body’s metabolic activity by employing positron- emitting radioactive isotopes

PET Scanner noninvasively generates 3D images of the distribution of an IV administered radiopharmaceutical within the body

Images enable evaluation of physiological phenomena that include

Glucose metabolism Oxygen metabolism Cerebral blood flow Receptor sites in brain

History Of PET Scan- The Milestones

Ernest O. Lawrence (early1930s) ,University of California, at Berkley laboratory invented the cyclotron

In 1953,Gordon Brownell at MIT created a precursor to the up coming PET scanner

PC – I was the first tomographic imaging device , designed in 1968 , completed in 1969 and reported in 1972

Subsequently PC-II and its commercial version were developed

In the early 1970s , the researches realized role of PET in assessing human brain function and the most favored technique was blood flow measurement with radiopharmaceutical, O-15 water

History Of PET Scan- The Milestones contd…

Louis Sokoloff and colleagues, and Al Wolf and Joanna Fowler (1976), developed fluorodeoxyglucose with Fluorine-18 (FDG)- expanding the scope of PET imaging

James Robertson(1973) proposed the ring system in PET scanning which produced high resolution images without motion ( PCR-I & PCR-II)

In the year 2000, David Townsend (physicist at the University of Geneva ,Switzerland) , and Ronald Nutt, electrical engineer ,introduced the PET/CT scanner, fusion of a state-of-the-art PET scanner and a fast, multidetector spiral CT scanner

The PET/CT scanner featured in Time magazine that year as “Invention of the Year

History Of PET Scan- The Milestones contd…

How does it work ?

A positron-emitting radioisotope is administered intravenously

Radiopharmaceutical gets distributed through the body via blood circulation, accumulating in the organs or body systems being studied

Radioisotope decays, emitting positrons

A positron (e+), the antimatter equivalent of an electron, collides with one of the nearby electrons (e-) – ANNIHILATION

Results in a burst of electromagnetic energy - two 511-keV gamma rays 180 degrees apart

PET scanner detects the gamma rays using detectors

The scanner electronics determine which of the gamma rays are coincident and pairs them into coincident events

COINCIDENCE is determined by employing a time frame or ‘ coincidence window’- if two coincident gamma rays are detected on opposite sides of the patient’s body within nanoseconds of each other, the computer pairs and records them into coincident events

PET scanner collects all coincident events and sorts them into a sinogram

Sinogram is reconstructed with corrections by the computer to produce two- or three-dimensional images

Radioisotope tracer used Application11C(R)-PK11195 Activated microglia11C-Methionine Cellular amino acid uptake11C-Flumazenil Central benzodiazepine binding

H2 150 Cerebral blood flow18F-6-Flurodopa Dopamine storage

11C-SCH23390 Dopamine D1 receptor binding11C-Raclopride Dopamine D2 receptor binding

18F-2-deoxyglucose Glucose metabolism55Cobalt Inflammatory response

11C-Deprenyl Monoamine oxidase A binding11C-Diprenorphine Opiate receptor binding

11C-carfentanil Opiate receptor binding

18F-cyclofoxy Opiate receptor binding

15O2 Oxygen metabolism

Common PET radioisotope tracers & their Application

1. ROLE IN MOVEMENT DISORDERS

PARKINSON’S DISEASE

Diagnosis of PD in early stages. (FDOPA, can quantify the deficiency of dopamine synthesis and storage within presynaptic striatal nerve terminal.)

Heiss WD, Eur J Neurol.2004

Diagnosis of PD in preclinical stages in persons at risk

( Patients with early PD have low- fluorodopa F18 uptake in one putamen with preserved uptake in the caudate nucleus.)

Sawle GV, Arch Neurol.1994

Differentiation between PD with other movement disorders

Differentiation between PD and striatonigral degeneration by PET (carbon-11 labeled SCH23390) (SND patients showed mean 12,21, and 31% declines in the ratios of radioactivity in the caudate, anterior putamen and posterior putamen compared with that in the occipital cortex.

These ratios were not significantly altered in the PD patients)

Shinotoh H, JNNP,1993

Assessment of graft viability after embryonic dopamine cell implantation (a significant increase in FDOPA uptake in the putamen of the group receiving implants was observed )

Nakamura T et al , Ann Neurol. 2001

PET Finding in Parkinsonian syndromes

PET

Tracer

Parkinson’s

disease

PSP MSA CBGD

18 F

Dopa

Asymmetric reductionputamen>caudate

Symmetrical reductioncaudate=putamen

Symmetrical reductioncaudate=putamen

Asymmetric & equivalent reduction caudate=putamen

18 FDG Normal/raised in

Striatum,

Reduced in tempoparietal

cortex

Reduced in

Bilateral striatum and frontal cortices

Reduced in striatum, brainstem, and cerebellum

Asymmetric reduction in striatum, thalamus, frontal and temporoparietal cortices

DYSTONIA 18 FDG-PET studies show a decrease in regional cerebral glucose metabolism

in caudate & lentiform nucleus and in the frontal field of the mediodorsal thalamic nucleus

Karbe H et al ,Neurology.1992

HUTINGTON’S DISEASE Preclinical detection by demonstrating reduced caudate glucose utilisation in

persons at high risk for the disorder and thus confirm DNA studies

Hayden MR et al, Neurology.1987

2. ROLE IN DEMENTIA

Early diagnosis of Alzheimer's disease

Shows abnormalities in early stage and may even aid in preclinical diagnosis

Is superior to neuropsychological tests

Zamrini E, Neurobiol Aging.2004

For screening of AD in high-risk groups of asymptomatic patients( persons homozygous for epsilon 4 allele for apolipoprotien E )

Reiman EM , N Engl J Med.1996

in vivo imaging of amyloid peptide can help in diagnosis of AD in preclinical and prodromal phases

Sair III, Neuroradiology.2004

Detection of progressive Dementia

18 FDG- PET has a sensitivity of 93% and specificity of 76% in identifying progressive dementia in patients undergoing evaluation for cognitive impairment

Silverman DH et al, JAMA. 2001

PET has a sensitivity & specificty of 94% & 73% , respectively in identifying patients with neuropathologically confirmed AD

Silverman DH et al, JAMA. 2001

Differentiation between AD and Vascular Dementia

Mild or atypical cases of AD can be differentiated from VaD using 18FDG- PET

hypometabolism in temporoparietal & frontal association areas, but relative sparing of primary cortical areas, basal ganglia and cerebellum

In VaD, a different pattern characterized by scattered areas with reduction of regional cerebral glucose metabolism extending over cortical and subcortical areas

Meilke R et al, J Neural Transm Suppl.1998

Differentiation between AD and Dementia with Lewy bodies (DLB)

In DLB , regional cerebral glucose metabolism is reduced in temporoparieto-occipito association cortices and the cerebellar hemispheres, as against AD, where medial temporal and cingulate are affected

Imamura T et al, Neurosci.1997

Monitoring the effect of treatment with cholinesterase inhibitors in AD PET evaluation before and after therapy with Donepezil or Rivastigmine is

helpful in assessing the treatment benefits

These PET scan images show normal brain activity (left) and reduced brain activity caused by Alzheimer's disease (right). The diminishing of the intense white and yellow areas in the image on the right indicates mild Alzheimer's disease, with the increase of blue and green colors showing decreased brain activity

Alzheimer’s disease Normal

3. ROLE IN STROKE

Identification of viable penumbra in acute ischemic stroke

Flumazenil( 11C) PET distinguishes between irreversibly damaged and viable penumbra tissue early after acute stroke

Heiss WD et al, Stroke.2000

Differentiation between recent and old stroke in patients with recuurent ischemic strokes

Recently infarcted areas, less than 2-month old, have a high Cobalt(55 Co) uptake ratio, whereas infarcts of 6 months to 1yr have an uptake ratio comparable to normal brain tissue

De Reuck et al, Clin Neurol Neurosurg.1999

Predicting probability of cortical infarction in acute ischemic stroke FMZ PET carries a lower probability of false positive reaction in comparison to

DWI MRI

Heis WD et al , Stroke.2004

Prediction of engraftment of neuronal implantation in chronic stroke FDG-PET has been used to map metabolic response to neuronal cell

implantation in the human neuroimplantation trial for stroke

Meltzer CC et al , Neurosurgery.2001

Demonstration of Diaschisis

De Reuck J et al, Acta Neurol Belg.1997

4. ROLE IN BRAIN TUMORS

Diagnostic assessment of cerebral gliomas Combined use of fluroethyl-l-tyrosine(FET) PET and MRI has a sensitivity of

93% & speficity of 94% for detection of tumor tissue

Pauleit D et al, Brain.2005

Grading of brain tumors FET- PET can differentiate between malignant and benign lesions of the brain High & low grade gliomas exhibit different uptake kinetics of FET

Wekesser M et al, Eur J Nucl Med Mol Imaging. 2005

Differentiation between tumor recurrence and radiation necrosis

11C-Methionine PET is useful

Tsuyuguchi N et al (J Neurosurg, 2003) sensitivity of 77.8% & specificity of 100%

Combined use of 11C-Methionine and FDG-PET enhances the accuracy of discrimination

Ogawa T et al, Acta Radiol.1991

Higher glucose metabolism in cerebral lymphomas also help to distinguish it from cerebral infections (toxoplasmosis & tuberculomas ) in patients with AIDS O’ Doherty MJ et al, J Nucl Med. 1997

5. ROLE IN EPILEPSY

Presurgical evaluation & localisation of epileptogenic foci

epileptogenic focus : decreased glucose metabolism and blood flow interictaly

the rates of lesion localisation by MR, ictal SPECT, and interictal FDG-PET was 60%, 70%, & 78% , resp.

Hwang SI, Am J Neuroradiol. 2001

obviates the need for invasive electrophysiological monitoring in most instances Cummings TJ, Neurosurg Clin N Am.1995

Temporal lobe epilepsy Deuterium-Deprenyl PET helps in identification of the epileptogenic temporal

lobe

Kumlien E, Epilepsia. 1995

Seizure lateralization with qualitative MR is inferior to qualitative PET Helveston W, Am J Neuroradiol. 1996

Routine diagnosis of epilepsy is more sensitive than MRI

Abnormalities of PET are detected in about 40% of those pts who have supposedly normal brain MRI

Swartzz BE, Mol Imaging Biol.2002

Treatment & outcome Alpha methyl-L-tryptophan(AMT) PET identifies nonresected epileptic cortex

in patients with failed neocortical epilepsy surgery

Juhasz C , Epilepsia. 2004

Prediction of postoperative outcome FDG-PET interictal metabolic pattern predicts seizure outcome at 2yrs after

surgery in pts with medial TLE

Dupont S, Arch Neurol.2000

A combination of MR & PET identifies 95% of pts with good outcome post epilepsy surgery

Heinz R, Am J Neuroradiol. 1994

6. MISCELLANEOUS

HEADACHE increased blood flow in midline brainstem structures during the headache

phase, persists even after treatment- reflecting activity of migraine centre

Diener HC, Headache. 1997

CHRONIC FATIGUE SYNDROME FDG-PET - hypometabolism in the right mediofrontal cortex & brainstem .

Brainstem hypometabolism seems to be a specific marker for in vivo diagnosis of CFS

Tirelli U, Am J Med. 1998

ENCEPHALITIS Rasmussen’s encephalitis- FDG-PET increases the diagnostic confidence in pts whose MR findings are

subtle or distributed bilaterally

Fiorella DJ, Am J Neuroradiol. 2001

to study the neuroinflammation in RE in vivo , aid in the selection of appropriate biopsy sites and assess the response to anti-inflammatory therapeutic agents

Paraneoplastic encephalitis(PNE) FDG-PET has shown positive findings in a case of PNE , associated with

Cystic teratoma, where MR was negative . PET may be superior to MR in some cases of PNE

Dadparvar S , Clin Nucl Med. 2003

MULTIPLE SCLEROSIS

Quantative cerebral abnormalities detected by FDG-PET- marker of disease activity in understanding the pathophysiological expression and therapeutic response of MS

Bakshi R, J Neuroimaging. 1998

Cobalt-PET - for assessing the disease progression rate in relapsing progressive-MS

Jansen HM, J Neurol Sci. 1995

LIMITATIONS

Major limitation of PET is lack of availability and cost

Technical limitations, relatively high incidence of false-positive reports, reduces its specificity

Specially trained personnel are required to interpret the reports

Not a good imaging test in isolation

Cyclotron is required (for generating radio-isotopes)

POTENTIAL FUTURE APPLICATIONS

Mainstay of clinical application in neurology is in the domains of Epilepsy surgery and Neuro-oncology

Early diagnosis of brain metastasis; distinguishing local recurrences from radiotherapy induced changes; and detecting malignant transformation of low grade tumours

Preoperative localisation of seizure foci in potential candidates for epilepsy surgery, especially in those with equivocal MRI findings

As an adjunct to clinical diagnosis in atypical cases of parkinsonian syndromes and dementia

Early and presymptomatic diagnosis of individuals at risk for neurodegenerative disorders such as AD and PD if an effective neuroprotective agent becomes available

In vivo amyloid imaging in AD

Prediction of engraftment of neuronal implantation in chronic stroke

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